Improving our understanding of childhood psoriasis: Identifying opportunities for early intervention for the prevention of long-term harm

1.1 Introduction Psoriasis is an immune-mediated chronic inflammatory disease affecting the skin and joints of adults and children. This PhD focused on psoriasis in children because it is especially for this age group that both a research need and an opportunity to improve long-term health outcomes exist. There is a deficiency of paediatric specific research to guide optimal management and, for many individuals, the persistence of psoriasis into adulthood has a negative cumulative effect over their lifetime. Difficulties can arise because of the physical, psychological, and social burden of psoriasis, including the development of psoriatic arthritis. 1.2 Research aim The aim of this research was to identify opportunities to intervene early in the disease course of children with psoriasis and juvenile psoriatic arthritis, in order to prevent long-term harm from these conditions. Specifically the research aims of each study were: 1. To determine current clinical practice in the assessment and management of childhood psoriasis. 2. To understand current clinical practice in the assessment of juvenile psoriatic arthritis and psoriasis. 3. To map the evidence and identify research gaps in the epidemiology of childhood psoriasis. 4. To identify studies which have developed or validated diagnostic criteria for psoriasis. 5. To derive expert agreed diagnostic criteria for plaque psoriasis in children. 6. To design a diagnostic accuracy study to develop DIagnostic criteria for PSOriasis in Children (DIPSOC Study) 1.3 Methods The initial studies focused on identifying deficiencies in current practice and exploring barriers in the detection of psoriasis and juvenile psoriatic arthritis. This research was undertaken as a multi-centre audit and case-note review, and qualitative descriptive interviews with paediatric rheumatologists and dermatologists. Framework and thematic content analysis were used to ascertain and explore the approach clinicians’ take to assess skin and joint disease. The subsequent studies have mapped the volume, nature, and characteristics of epidemiological studies and appraised the literature to inform the development of diagnostic criteria for psoriasis in children. This research was undertaken as a scoping review on the epidemiology of childhood psoriasis and a systematic review on diagnostic criteria for psoriasis. The studies in the systematic review were appraised for risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. The final studies focused on developing diagnostic criteria for psoriasis in children. An electronic Delphi (eDelphi) consensus study with the International Psoriasis Council (IPC) used sequential online questionnaires and scoring to reach agreement on a list of expert-derived criteria. These five studies informed the design of a multi-centre case-control diagnostic accuracy study (DIPSOC study) to test the consensus agreed criteria and develop the best predictive criteria. 1.4 Results The audit of the care of 285 children with psoriasis showed that compliance with national guidelines was variable. Only half of children were assessed annually for juvenile psoriatic arthritis and a third of children with psoriasis were potentially misdiagnosed with having other skin diseases in primary care. Exploring this further, paediatric rheumatologists’ and dermatologists’ current approach for assessing skin and joint disease, respectively, may not detect psoriasis and juvenile psoriatic arthritis. Reviewing the evidence base, most epidemiological data originates from case-series and cross-sectional studies, and there were few case-control and cohort studies investigating risk factors for disease onset, comorbidities, and long-term health outcomes in paediatric psoriasis. This work highlighted a need to improve the recognition of psoriasis in children and for new studies using standardised methodologies and definitions. Currently, no clinical examination-based diagnostic criteria for psoriasis have been developed, tested, or validated. To address this evidence gap, experts collectively agreed on 16 diagnostic features, divided into three major and thirteen minor criteria, which are important for the clinical diagnosis of plaque psoriasis in children. These consensus agreed criteria will be tested in the DIPSOC study. The design of DIPSOC aims to minimise bias in the four key domains proposed by the QUADAS-2 tool, but uses a case-control design to ensure the recruitment target is feasible within the resources available. 1.5 Discussion The research in this PhD makes an important contribution to the field of paediatric psoriasis and culminates in the design of the DIPSOC study to test and refine a list of diagnostic criteria for psoriasis in children. The criteria are intended to improve the recognition and early diagnosis of psoriasis in children, as well as offer a standardised disease definition for clinical trials and observational research. Improved diagnostic accuracy and increasing the quality of evidence from research studies will provide opportunities for early intervention to prevent long-term harm in children with psoriasis

Improving our understanding of childhood psoriasis: Identifying opportunities for early intervention for the prevention of long-term harm

1.1 Introduction Psoriasis is an immune-mediated chronic inflammatory disease affecting the skin and joints of adults and children. This PhD focused on psoriasis in children because it is especially for this age group that both a research need and an opportunity to improve long-term health outcomes exist. There is a deficiency of paediatric specific research to guide optimal management and, for many individuals, the persistence of psoriasis into adulthood has a negative cumulative effect over their lifetime. Difficulties can arise because of the physical, psychological, and social burden of psoriasis, including the development of psoriatic arthritis. 1.2 Research aim The aim of this research was to identify opportunities to intervene early in the disease course of children with psoriasis and juvenile psoriatic arthritis, in order to prevent long-term harm from these conditions. Specifically the research aims of each study were: 1. To determine current clinical practice in the assessment and management of childhood psoriasis. 2. To understand current clinical practice in the assessment of juvenile psoriatic arthritis and psoriasis. 3. To map the evidence and identify research gaps in the epidemiology of childhood psoriasis. 4. To identify studies which have developed or validated diagnostic criteria for psoriasis. 5. To derive expert agreed diagnostic criteria for plaque psoriasis in children. 6. To design a diagnostic accuracy study to develop DIagnostic criteria for PSOriasis in Children (DIPSOC Study) 1.3 Methods The initial studies focused on identifying deficiencies in current practice and exploring barriers in the detection of psoriasis and juvenile psoriatic arthritis. This research was undertaken as a multi-centre audit and case-note review, and qualitative descriptive interviews with paediatric rheumatologists and dermatologists. Framework and thematic content analysis were used to ascertain and explore the approach clinicians’ take to assess skin and joint disease. The subsequent studies have mapped the volume, nature, and characteristics of epidemiological studies and appraised the literature to inform the development of diagnostic criteria for psoriasis in children. This research was undertaken as a scoping review on the epidemiology of childhood psoriasis and a systematic review on diagnostic criteria for psoriasis. The studies in the systematic review were appraised for risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. The final studies focused on developing diagnostic criteria for psoriasis in children. An electronic Delphi (eDelphi) consensus study with the International Psoriasis Council (IPC) used sequential online questionnaires and scoring to reach agreement on a list of expert-derived criteria. These five studies informed the design of a multi-centre case-control diagnostic accuracy study (DIPSOC study) to test the consensus agreed criteria and develop the best predictive criteria. 1.4 Results The audit of the care of 285 children with psoriasis showed that compliance with national guidelines was variable. Only half of children were assessed annually for juvenile psoriatic arthritis and a third of children with psoriasis were potentially misdiagnosed with having other skin diseases in primary care. Exploring this further, paediatric rheumatologists’ and dermatologists’ current approach for assessing skin and joint disease, respectively, may not detect psoriasis and juvenile psoriatic arthritis. Reviewing the evidence base, most epidemiological data originates from case-series and cross-sectional studies, and there were few case-control and cohort studies investigating risk factors for disease onset, comorbidities, and long-term health outcomes in paediatric psoriasis. This work highlighted a need to improve the recognition of psoriasis in children and for new studies using standardised methodologies and definitions. Currently, no clinical examination-based diagnostic criteria for psoriasis have been developed, tested, or validated. To address this evidence gap, experts collectively agreed on 16 diagnostic features, divided into three major and thirteen minor criteria, which are important for the clinical diagnosis of plaque psoriasis in children. These consensus agreed criteria will be tested in the DIPSOC study. The design of DIPSOC aims to minimise bias in the four key domains proposed by the QUADAS-2 tool, but uses a case-control design to ensure the recruitment target is feasible within the resources available. 1.5 Discussion The research in this PhD makes an important contribution to the field of paediatric psoriasis and culminates in the design of the DIPSOC study to test and refine a list of diagnostic criteria for psoriasis in children. The criteria are intended to improve the recognition and early diagnosis of psoriasis in children, as well as offer a standardised disease definition for clinical trials and observational research. Improved diagnostic accuracy and increasing the quality of evidence from research studies will provide opportunities for early intervention to prevent long-term harm in children with psoriasis

Where are we with developing diagnostic criteria for skin diseases? Mapping the evidence in 2021

The breadth and scope of dermatological diagnostic criteria is currently unknown. We created a map of diagnostic criteria to provide a panoramic view of past and ongoing research to develop dermatological diagnostic criteria. We analysed studies for which the primary research aim was to develop, validate or critically appraise diagnostic criteria for dermatological conditions identified with a PubMed search conducted in July 2021. The researched skin diseases were grouped based on similarities in pathogenesis. In total, 166 studies covering 104 skin diseases were included in the data extraction. The two largest disease categories were autoimmune diseases (17%) and rare disorders and genetic syndromes (17%). Of the total studies analysed, 28% included a type of validation and 64% provided diagnostic accuracy data. This map of diagnostic criteria covers a vast range of dermatological conditions, but many common skin diseases were under-represented. We plan to update the map and make it available for all health professionals and researchers

Early recognition and detection of juvenile psoriatic arthritis: a call for a standardized approach to screening

Background: National Institute for Health and Care Excellence (NICE) guidelines recommend annual screening for psoriatic arthritis (PsA) in all patients with psoriasis. Currently, no validated assessment tools have been recommended for screening for juvenile PsA (JPsA). Aim: To determine dermatologists' practice when assessing children's joints and explore the challenges dermatologists experience when looking for joint disease, in order to inform future strategies to improve early detection of arthritis. Methods: Structured telephone interviews were undertaken with dermatologists identified through the British Society of Paediatric Dermatology. Percentages for binary and categorized responses were calculated. Thematic content analysis was used to generate a set of core themes across the interview data. Results: Of the 41 consultant dermatologists contacted, 23 agreed to be interviewed. Of these, 78% (18/23) reported they routinely ask about joint disease. Only 13% (3/23) routinely examine the joints of children with psoriasis. Overall, assessment for JPsA lacked a structured, evidence-based approach. The average confidence rating for assessing joint disease was low (score of 3). The two key barriers described for detecting arthritis were a lack of experience and training, and subtle or difficult to detect signs. The two main suggestions for improving detection were the introduction of an assessment tool/guideline and increased clinical experience and training. Conclusion: There is a clear need for dermatologists to use a standardized approach for screening and to increase their confidence in paediatric musculoskeletal examination. In this article, we provide guidance on screening for psoriatic arthritis in children based on our clinical experience

Putting UK DCTN studies into practice: a nurse and patient perspective of the investigator day for the BLISTER and STOP GAP trials

The BLISTER and STOP GAP studies are two important trials in the field of dermatology and also for the UK Dermatology Clinical Trials Network (UK DCTN) as a collaborative network. They make a significant contribution to our limited evidence base for the management of bullous pemphigoid and pyoderma gangrenosum respectively. In keeping with the priorities of the UK DCTN, both trials investigated treatments routinely available in dermatology and focused on rarer skin diseases which benefited from involvement of the network to recruit a sufficient number of patients. The ‘Putting UK DCTN Studies into Practice Event’ was an opportunity for clinicians, patients and researchers involved to share their experiences of the studies and the related skin conditions. Investigators from both trials commented on their experiences and how being involved in the BLISTER and STOP GAP trials had affected their attitude to research and changed their clinical practice. In this article we hope to continue the ethos of a shared experience by providing an insight of the investigator day from a nursing and patient perspective

Long-term topical corticosteroid use and risk of skin cancer: a systematic review protocol

Review question/objective: The objective of this systematic review is to synthesize the best available research evidence to determine the risk of skin cancer in patients on long-term use of topical corticosteroids. Specifically the review question is: In people using long-term (regular use over one month) topical corticosteroids, what is the risk of developing skin cancer (clinically or histologically confirmed basal cell carcinoma, squamous cell carcinoma or melanoma)

The epidemiology of childhood psoriasis: a scoping review

Psoriasis is an inflammatory noncommunicable skin disease that affects both adults and children. At present, the epidemiology and natural history of psoriasis are not widely understood. This scoping review aimed to map the existing literature on the epidemiology of childhood psoriasis, identify research gaps for future studies and provide a comprehensive, clinically useful review. Search strategies were developed for Ovid Medline, Ovid Embase, Google Scholar and hand searching. In total, 131 articles met the inclusion criteria and were mapped; 107 articles were included for data extraction. Over the last 25 years there has been a dramatic increase in the volume of published observational epidemiological studies on childhood psoriasis. The majority were case series or cross-sectional studies, concentrated in Europe, Asia and North America. The prevalence of childhood psoriasis was found to be higher in European countries, older children and girls. Up to 48·8% of children had a family history of psoriasis in a first-degree relative. The most frequent subtype was plaque psoriasis and the most common initial sites of presentation were the scalp, limbs and trunk. Specific genetic differences have been found between child-onset and adult-onset populations. Case–control and cohort studies investigating risk factors for psoriasis onset, comorbidities and long-term health outcomes were extremely limited. The choice of study design and heterogeneity in methodology limit the validity and generalizability of the information, consistency of the results, and comparability of the studies. Well-designed epidemiological studies are needed to provide precise and consistent information about the frequency and clinical presentation, risk factors, associated diseases and long-term outcomes in childhood psoriasis

Long-term topical corticosteroid use and risk of skin cancer: a systematic review

Objective: The objective of this systematic review was to synthesize available research evidence to determine the risk of skin cancer in patients with long-term use of topical corticosteroids (TCS). Introduction: Topical corticosteroids are one of the most commonly prescribed medicines in dermatology and the mainstay of the treatment of atopic dermatitis and other skin conditions such as psoriasis. They are often required for months or years to control the disease and ultimately restore patients’ quality of life. In some patients, TCS may have a local immunosuppressive effect and theoretically increase the risk of skin cancer, whilst on the other hand TCS may decrease the risk of skin cancer in patients where TCS are used to treat inflammatory skin disease. To date, no systematic review has been performed to collate evidence on the effect of long-term TCS use on the risk of skin cancer. Inclusion criteria: This review considered studies that included people of all ages, genders and ethnicities, including HIV and transplant participants or participants with genetic diseases (for example, Gorlin-Goltz syndrome) This review considered studies that evaluated long-term use of topical corticosteroids. “Long-term” was defined as using TCS more than once a week for a month or longer. The review included cohort, cross-sectional and case-control observational studies exploring the association between the stated intervention and outcomes. The primary outcome measures of interest were: non-melanoma skin cancer (keratinocyte carcinoma), cutaneous squamous cell carcinoma (cSSC), basal cell carcinoma (BCC) or melanoma skin cancer. Genital and oral skin cancers are considered to be slightly different so we did not include them in this review. Methods: We performed a comprehensive search of MEDLINE, Embase and LILACS on November 9, 2017 to identify observational epidemiological studies assessing the association between long-term TCS use and skin cancer. We also searched EThOS at the British Library and three drug safety databases to identify unpublished work. The titles, abstracts and full text identified from the search were assessed independently by two authors against pre-specified inclusion/exclusion criteria. Methodological quality was not assessed as no articles were found which met the inclusion criteria. Data extraction was not possible as no articles were found which met the inclusion criteria. It was not possible to complete data synthesis as no articles were found which met the inclusion criteria. Results: A total of 1703 potentially relevant studies were identified following a comprehensive electronic search. After abstract and title screening, 51 full texts were assessed for eligibility criteria. Of these, no study met the inclusion criteria. No additional records were identified from searching unpublished literature. Conclusions: We did not find any studies that could help us establish if long-term TCS use is associated with skin cancer. Future research using primary care databases might give a better understanding regarding long-term use of TCS and skin cancer

Quality of life in people with vitiligo: a systematic review and meta-analysis

Vitiligo is cosmetically disfiguring and has profound psychosocial effects due to stigmatization, problems in sexual function, anxiety, self-esteem and difficulty finding employment. Previous studies suggest a reduction in quality of life (QoL) due to vitiligo, but to date no systematic review has quantified this in comparison to people without vitiligo. Therefore, the aim of this review was to compare QoL in people with and without vitiligo

Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated

Background & Aims: The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers.Method: Between 2014-2021, adult patients diagnosed with rheumatoid arthritis (RA) or psoriasis for >−2 years were recruited prospectively from six UK sites. The MTX group included patients who received MTX for >−6 months, whereas the unexposed group included those who never received MTX. All patients underwent full liver profiling, with transient elastography (TE) and enhanced liver fibrosis (ELF) marker measurements.Results: A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness >−7.9 kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF >−9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most significant risk factor associated with liver stiffness >−7.9 kPa (adjusted odds ratio = 3.19; 95% CI 1.95–5.20; p −9.8 (odds ratio = 1.76; 95% CI 1.20–2.56; p = 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis.Conclusion: The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX